Dimethylformamide → Ethyl alpha-[3-(trifluoromethyl)benzylamino]-1-benzylindole-3-acetate

HRID 5605Notes

Reaction equation

HRID 5605 reaction equation
[F:1][C:2]([F:32])([F:31])[C:3]1[CH:4]=[C:5]([CH:28]=[CH:29][CH:30]=1)[CH2:6][NH:7][CH:8]([C:12]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[N:14]([CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH:13]=1)[C:9]([OH:11])=[O:10].C[O-].[Na+].[CH2:36](I)[CH3:37].CN(C)C=O>CO.CCOCC.[Cl-].[Na+].O>[F:32][C:2]([F:1])([F:31])[C:3]1[CH:4]=[C:5]([CH:28]=[CH:29][CH:30]=1)[CH2:6][NH:7][CH:8]([C:12]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[N:14]([CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH:13]=1)[C:9]([O:11][CH2:36][CH3:37])=[O:10]

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 6340IodoethaneHCID 10942334Sodium MethoxideHCID 53973377HCID 53973377, compound

Product 1

HCID 19796621Ethyl alpha-[3-(trifluoromethyl)benzylamino]-1-benzylindole-3-acetate

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 3283Diethyl EtherSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To a magnetically stirred suspension of α-[3-(trifluoromethyl)benzylamino)-1-benzylindole-3-acetic acid (21.9 g, 0.05 mol) in 250 mL of methanol at room temperature was treated with 11.34 g of sodium methoxide (25% in methanol) at once. The resulting solution was stirred for two hours, concentrated directly on a rotary evaporator and finally the resulting white residue was pumped down under high vacuum using a warm water bath at ca 50° C. The dry sodium salt was dissolved in 100 mL of dimethylformamide, charged at once with ethyl iodide (9.36 g, 0.06 mol, 1.20 eq) and stirred in the dark for 48 hours with an additional 50 mL of dimethylformamide being added after 20 hours to facilitate stirring of the gelantinous precipitate which formed. The contents were diluted with ether and poured into 125 mL of ice water plus 125 ml of saturated brine. The aqueous phase was separated from the organic layer and extracted once more with ether. The combined organic extracts were dried with anhydrous Na2SO4 and concentrated at reduced pressure. Flash chromatography with 250 g of silica gel packed and eluted with ethyl acetate-hexane (1:4) gave the title compound as a yellow oil.

Workup

  1. concentrationconcentrated directly on a rotary evaporator
  2. customat ca 50° C
  3. dissolutionThe dry sodium salt was dissolved in 100 mL of dimethylformamide
  4. additionadded after 20 hours
  5. stirringto facilitate stirring of the gelantinous precipitate which
  6. customformed
  7. customThe aqueous phase was separated from the organic layer
  8. extractionextracted once more with ether
  9. dry with materialThe combined organic extracts were dried with anhydrous Na2SO4
  10. concentrationconcentrated at reduced pressure
  11. washeluted with ethyl acetate-hexane (1:4)

Sources & evidence

ORD record
ord-5e05af3e4327470e88c75d53a7f6a7c7
Source dataset
uspto-grants-1993_09
Patent number
US05245046

Reaction notes

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